Bosnian Journal of Basic Medical Sciences

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ISSN / EISSN : 1512-8601 / 1840-4812
Current Publisher: Association of Basic Medical Sciences of FBIH (10.17305)
Total articles ≅ 1,090
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Chenhui Ma, Zelong Cui, Yichao Wang, Lei Zhang, Junye Wen, Huaibin Guo, Na Li, Wanxing Zhang
Bosnian Journal of Basic Medical Sciences; doi:10.17305/bjbms.2020.5096

Abstract:
Pancreatic cancer (PCC) is a common malignant tumor of the digestive system that is resistant to traditional treatments and has an overall 5-year survival rate of less than 7%. Transcriptomics research provides reliable biomarkers for diagnosis, prognosis and clinical precision treatment, as well as the identification of molecular targets for the development of drugs to improve patient survival. We sought to identify new biomarkers for PCC by combining transcriptomics and clinical data with current knowledge regarding molecular mechanisms. Consequently, we employed weighted gene co-expression network analysis and differentially expressed gene analysis to evaluate genes that are co-expressed in tumor versus normal tissues using pancreatic adenocarcinoma data from The Cancer Genome Atlas and dataset GSE16515 from the Gene Expression Omnibus. Twenty-one overlapping genes were identified, with enrichment of key Gene Oncology and Kyoto Encyclopedia of Genes and Genomes pathways, including epidermal growth factor receptor signaling, cadherin, cell adhesion, ubiquinone and glycosphingolipid biosynthesis pathways, and retinol metabolism. Protein-protein interaction analysis highlighted 10 hub genes according to Maximal Clique Centrality. Univariate and multivariate COX analyses indicated that TSPAN1 serves as an independent prognostic factor for PCC patients. Survival analysis distinguished TSPAN1 as an independent prognostic factor among hub genes in PCC. Finally, immunohistochemical staining results suggested that the TSPAN1 protein levels in the Human Protein Atlas were significantly higher in tumor tissue than in normal tissue. Therefore, TSPAN1 may be involved in PCC development and act as a key biomarker for the diagnosis and prediction of PCC patient survival.
Bosnian Journal of Basic Medical Sciences; doi:10.17305/bjbms.2020.5219

Abstract:
RASSF1A represents one of the eight isoforms of the RASSF1 gene. RASSF1A is a tumor suppressor gene whose inactivation influences tumor initiation and development. In cancer, RASSF1A is frequently inactivated by mutations, loss of heterozygosity and, most commonly, by promoter hypermethylation. As epigenetic inactivation of RASSF1A was detected in various cancer types, it was extensively investigated and nowadays, the research on RASSF1A promoter methylation proceeds in the light of an epigenetic tumor biomarker. Analyses of DNA methylation of genes involved in carcinogenesis such as RASSF1A are currently done mostly on genomic DNA (gDNA). Simultaneously, cell-free DNA (cfDNA) from liquid biopsies has lately been developed as an early cancer diagnostic tool. This review discusses the evidence on aberrantly methylated RASSF1A in gDNA and cfDNA from different cancer types and its utility for early cancer diagnosis, prognosis, and surveillance. Furthermore, methylation frequencies of RASSF1A in gDNA and cfDNA were compared in various cancer types. The weaknesses and strengths of the investigations mentioned above are discussed. In conclusion, although the importance of RASSSF1A methylation in relation to cancer was established, and it became included in several diagnostic panels, the evidence of its diagnostic utility is still experimental and not yet implemented in standard clinical health care.
Comment
Nuri Kose, Tarık Yıldırım, Fatih Akın, Seda Elçim Yıldırım, Ibrahim Altun
Bosnian Journal of Basic Medical Sciences; doi:10.17305/bjbms.2020.5292

Abstract:
We appreciate the comments made by Dr Bedel and colleagues. NLR, PLR and LMR are affected by various diseases such as oncological, collagen tissue, inflammatory, or severe renal/liver diseases [1]. Because of this, we have listed some of the above-mentioned disorders in the tables. Hematological diseases, collagen tissue disease, inflammatory diseases, congenital heart disease, or severe renal/liver disease were therefore excluded from the study. However, the presence of malignancy did not affect our results in regression analysis.Platelets swell until 120 minutes in ethylene diamine tetra acetic (EDTA) and until 60 minutes in citrate [2]. Authors suggest that optimal measuring time should not exceed 120 minutes. The blood samples of the patients were taken within 1 hour after their emergency admission. All blood samples in our study were tested within 1 hour of collection [3]. We used EDTA for whole blood anticoagulation. The mean duration of symptoms prior to admission was 5.04 ± 6.9 days. The drugs such as corticosteroids affect inflammatory parameters. Therefore, we excluded inflammatory diseases without emphasizing corticosteroids or other anti-inflammatory drugs.
Comment
Cihan Bedel, Mustafa Korkut, Hamit Hakan Armağan
Bosnian Journal of Basic Medical Sciences; doi:10.17305/bjbms.2020.5236

Abstract:
We read with great interest the article “Prognostic role of NLR, PLR, and LMR in patients with pulmonary embolism” by Köse et al.[1]. They found that the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR) were related to the prognosis and clinical severity of patients with pulmonary embolism (PE). First of all, we congratulate the authors for their invaluable contribution to literature. However, we think that there are some points that should be discussed regarding the use of these laboratory parameters. White blood cell subtypes NLR, PLR, and LMR have been associated with many inflammatory diseases, including PE [2,3]. These parameters, which can be easily determined by simple and easy measurement of systemic inflammation, maintain their importance today. However, these parameters are affected by many factors such as trauma, local or systemic infection, acute coronary syndromes, and malignancy [3-5]. For these reasons, it would be better for the authors to mention these factors and exclude them from the tables that included malignancy and trauma patients in the study. It is known that drugs including steroids can increase neutrophils and decrease lymphocytes and therefore affect NLR, PLR and LMR values [6]. Therefore, it will be more valuable to exclude patients who use drugs that may affect laboratory parameters. In addition, plasma inflammatory biomarkers are time dependent variables, the time of sample collection and the time from the onset of the symptom to the sampling may have an impact on the parameters [3-6]. Therefore, it is important to identify the time from first symptom to sample collection and the factors that may affect it. In conclusion, because NLR, PLR and LMR can be affected by many factors, prospective studies with large populations are needed to show the accuracy of use in critically ill patients.
Amra Sakusic, Dragana Markotic, Yue Dong, Emir Festic, Vladimir Krajinovic, Alan Sustic, Natasa Milivojevic, Milka Jandric, Srdjan Gavrilovic, Alexander Niven, et al.
Bosnian Journal of Basic Medical Sciences; doi:10.17305/bjbms.2020.4934

Abstract:
In many areas of the world, critical care providers caring for COVID-19 patients lacked specific knowledge and were exposed to the abundance of new and unfiltered information. With support from the World Health Organization, we created a multimodal tele-education intervention to rapidly share critical care knowledge related to COVID-19 targeting providers in a region of Southeastern Europe. We delivered 60-minute weekly interactive tele-education sessions over YouTube TM between March and May 2020, supplemented by a dedicated webpage. The intervention was reinforced using a secure social media platform (Viber TM) providing continuous rapid knowledge exchange among faculty and learners. A high level of engagement was observed with over 2,000 clinicians participating and actively interacting over a six-week period. Surveyed participants were highly satisfied with the intervention. Tele-education interventions using social media platforms are feasible, low-cost, and effective methods to share knowledge during the COVID-19 pandemic.
Ryan D'souza, Christopher Duncan, Daniel Whiting, Michael Brown, Matthew Warner, Hugh Smith, Hilal Kremers, Thomas Stewart
Bosnian Journal of Basic Medical Sciences; doi:10.17305/bjbms.2020.5060

Abstract:
Tranexamic acid (TXA) reduces blood loss and transfusion rates in unilateral total knee arthroplasty (TKA), but there is limited data regarding its efficacy in bilateral TKA. This study reports the impact TXA has on clinical outcomes and hospital cost of care in simultaneous, primary bilateral TKA. The 449 patients were retrospectively reviewed. Primary outcomes included the rates of allogeneic and autologous blood transfusion. Secondary outcomes included hospital length of stay (HLOS), post-hospital discharge disposition, 30-day thromboembolic events (TEE), and mean hospital cost of care. Total direct medical costs were obtained from an institutional research database and adjusted to nationally representative unit costs in 2013 inflation-adjusted dollars. Our study revealed that in patients undergoing simultaneous bilateral TKA, TXA use was associated with reduced allogeneic (OR 0.181, 95% CI 0.090-0.366, p
Mirsada Hukic, Mirza Ponjavic, Emin Tahirovic, Almir Karabegovic, Elvir Ferhatbegovic, Maja Travar, Fadila Serdarevic
Bosnian Journal of Basic Medical Sciences; doi:10.17305/bjbms.2020.5081

Abstract:
Between March 5 and July 25, 2020, the total number of SARS-CoV-2 confirmed cases in Bosnia and Herzegovina (BH) was 10 090 corresponding to a cumulative incidence rate of 285.7 per 100 000 population. Demographic and clinical information on all the cases along with exposure and contact information was collected using a standardized case report form. In suspected SARS-CoV-2 cases, respiratory specimens were collected and tested by real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) assay. The dynamic of the outbreak was summarized using epidemiological curves, instantaneous reproduction number Rt and interactive choropleth maps for geographical distribution and spread. The rate of hospitalization was 14.0 % (790/5646) in Federation of Bosnia and Herzegovina (FBH) and 6.2 % (267/4299) in Republic of Srpska (RS). The death rate was 2.2% (122/5646) in FBH and 3.6% in the RS (155/4299). After the authorities lifted mandatory quarantine restrictions, the basic reproduction number increased from 1.13 on May, the 20th to 1.72 on May the 31st. The outbreak concerns both entities, Federation of Bosnia and Herzegovina and Republika Srpska, and it is more pronounced in those aged 20-44 years. It is important to develop the communication and emergency plan for the SARS-CoV-2 outbreak in BH, including the mechanisms to allow the ongoing notification and updates at the national level.
Xu Feng, En-Shi Xu
Bosnian Journal of Basic Medical Sciences; doi:10.17305/bjbms.2020.5066

Abstract:
Most advanced non-small cell lung cancer (NSCLC) patients are accompanied by brain metastasis which is the major cause of increased mortality. The fusion rearrangement of anaplastic lymphoma kinase (ALK) gene is an important feature of brain metastasis in lung cancer. The novel ALK inhibitors alectinib and lorlatinib are shown to be effective against NSCLC brain metastasis, while their underlying mechanism of action is unclear. Epithelial–mesenchymal transition (EMT) proteins and matrix metalloproteinases (MMPs) play important roles in brain metastasis by regulating the blood-brain barrier (BBB). To reveal the molecular function of alectinib and lorlatinib, we explored their effects on the cellular levels of EMT markers: VIM and FN1 and the matrix metalloproteinases MMP-9 and MMP-7. The mRNA and protein levels of VIM, FN1, MMP-9, and MMP-7 were elevated in H3122 cells. However, upon alectinib and lorlatinib treatment the levels were significantly reduced. Similar results were obtained when these experiments were performed either in a dose dependent or time dependent manner. Furthermore, alectinib and lorlatinib also inhibited the cell viability and migration of H3122 cells. Interestingly, in comparison to individual drugs, the combination of alectinib and lorlatinib was found to be substantially more effective. Overall, these results suggest that alectinib and lorlatinib possibly function via the downregulation of MMPs and EMT in NSCLC metastasis.
Deligonul Adem, Serkan Yazici, Mine Ozsen, Sibel Kahraman Cetintas, Ulviye Yalcinkaya, Ahmet Bilgehan Şahin, Ozgur Tanrıverdi, Sibel Oyucu Orhan, Birol Ocak, Erdem Cubukcu, et al.
Bosnian Journal of Basic Medical Sciences; doi:10.17305/bjbms.2020.5088

Abstract:
Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft tissue sarcoma that originates from the dermis or subcutaneous tissue in the skin. While its prognosis is generally favorable, disease recurrence is relatively frequent. Because morbidity after repeated surgery may be significant, an optimized prediction of recurrence-free survival (RFS) has the potential to improve current management strategies. The purpose of this study was to investigate the prognostic value of the Ki-67 proliferation index with respect to RFS in patients with DFSP. We retrospectively analyzed data from 45 patients with DFSP. We calculated the Ki-67 proliferation index as the percentage of immunostained nuclei among the total number of tumor cell nuclei regardless of the intensity of immunostaining. We constructed univariate and multivariate Cox proportional hazards regression models to identify predictors of RFS. Among the 45 patients included in the study, 8 developed local recurrences and 2 had lung metastases (median follow-up: 95.0 months; range: 5.2−412.4 months). The RFS rates at 60, 120, and 240 months of follow-up were 83.8%, 76.2%, and 65.3%, respectively. The median Ki-67 proliferation index was 14%. Notably, we identified the Ki-67 proliferation index as the only independent predictor for RFS in multivariate Cox proportional hazards regression analysis (hazard ratio = 1.106, 95% confidence interval = 1.019−1.200, p = 0.016). In summary, our results highlight the potential usefulness of the Ki-67 proliferation index for facilitating the identification of patients with DFSP at higher risk of developing disease recurrences.
Stasa Krasic, Sergej Prijic, Predrag Minic, Gordana Petrovic, Dejan Nesic, Vladislav Vukomanovic
Bosnian Journal of Basic Medical Sciences; doi:10.17305/bjbms.2020.5037

Abstract:
The novel coronavirus disease (COVID-19) may induce multisystem inflammatory syndrome in children, which may be associated with Kawasaki-like disease, and cardiac injury. In this study, we presented three male adolescents with multisystem inflammatory syndrome and myocardial injury admitted to the hospital during the peak of COVID-19 pandemic. All of the three patients had a history of fever, gastrointestinal symptoms, polymorph rash, non-exudative conjunctivitis, and signs of acute myocarditis. One of them had renal failure. Previously, they did not have an acute infection. Upon admission, they were hypotensive and tachycardic. A nasopharyngeal swab for SARS-CoV-2 on reverse transcription-polymerase chain reaction (PCR) assay was negative, but neutralizing viral antibodies were positive. In combination with blood tests, ECG, echocardiography and computerized tomography (CT), a multisystem inflammatory syndrome associated with acute myocarditis with mild to moderate systolic dysfunction and dilated coronary arteries were diagnosed. Two of three patients had shock syndrome and required inotropic support. All patients were treated with intravenous immunoglobulins. The second patient had a fever up to 102.2°F (39°C) three days after intravenous immunoglobulins. Further, he was treated according to protocols for refractory Kawasaki disease, with an intravenous methylprednisolone pulse therapy and aspirin. After a few hours, he became afebrile and the clinical signs disappeared. The favorable short-term outcome may reflect the early recognition and adequate therapy; however, the long-term outcomes are currently unknown.
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